Increasing skeletal muscle carnitine content in older individuals increases whole-body fat oxidation during moderate-intensity exercise.

Intramyocellular lipid (IMCL) utilization is impaired in older individuals, and IMCL accumulation is associated with insulin resistance. We hypothesized that increasing muscle total carnitine content in older men would increase fat oxidation and IMCL utilization during exercise, and improve insulin sensitivity. Fourteen healthy older men (69 ± 1 year, BMI 26.5 ± 0.8 kg/m2 ) performed 1 h of cycling at 50% VO2 max and, on a separate occasion, underwent a 60 mU/m2 /min euglycaemic hyperinsulinaemic clamp before and after 25 weeks of daily ingestion of a 220 ml insulinogenic beverage (44.4 g carbohydrate, 13.8 g protein) containing 4.5 g placebo (n = 7) or L-carnitine L-tartrate (n = 7). During supplementation, participants performed twice-weekly cycling for 1 h at 50% VO2 max. Placebo ingestion had no effect on muscle carnitine content or total fat oxidation during exercise at 50% VO2 max. L-carnitine supplementation resulted in a 20% increase in muscle total carnitine content (20.1 ± 1.2 to 23.9 ± 1.7 mmol/kg/dm; p < 0.01) and a 20% increase in total fat oxidation (181.1 ± 15.0 to 220.4 ± 19.6 J/kg lbm/min; p < 0.01), predominantly due to increased IMCL utilization. These changes were associated with increased expression of genes involved in fat metabolism (ACAT1, DGKD & PLIN2; p < 0.05). There was no change in resting insulin-stimulated whole-body or skeletal muscle glucose disposal after supplementation. This is the first study to demonstrate that a carnitine-mediated increase in fat oxidation is achievable in older individuals. This warrants further investigation given reduced lipid turnover is associated with poor metabolic health in older adults.

Excluding subarachnoid haemorrhage within 24 hours: to LP or not to LP?

BACKGROUND AND PURPOSE: Subarachnoid haemorrhage (SAH) is a potentially life-threatening cause of acute headache. Current conventional practice in the United Kingdom (UK) is for head computed tomography (CT) followed by cerebrospinal fluid (CSF) xanthochromia analysis if the head CT is normal. However, with increasing radiological accuracy, head CT alone may be sufficient to exclude SAH without requiring CSF xanthochromia for confirmation. This study aims to determine whether CSF xanthochromia is still required to confirm exclusion of SAH after normal head CT within a tertiary referral centre. METHODS: Data was obtained from Nottingham University Hospitals (NUH) NHS Trust databases on 999 patients presenting with symptoms suspicious of SAH from 2012 to 2015. All patients had CSF xanthochromia analysis when head CT was normal or inconclusive for suspected SAH. RESULTS: A total of 179 patients were diagnosed with SAH (17.9%). 176 patients were diagnosed radiologically and 3 patients required further investigations. The 3 of the 802 patients who underwent lumbar puncture (LP) and were identified as having had SAH presented more than 24 hours after ictus. When stratified according to the time of presentation, a normal CT head was observed in those who presented within 24 hours from ictus (sensitivity of 100% [95% CI 92.5-100] and negative predictive value of 100% [97.2-100]). CONCLUSION: Within a tertiary referral centre for SAH, a normal head CT has a very high negative predictive value to exclude SAH when carried out within 24 hours from ictus provided a 3rd generation CT scanner is utilised, and the scan is reported by a neuroradiologist. CSF xanthochromia analysis in this cohort may still be indicated in those presenting with a high clinical suspicion of SAH and in hospital settings where neuroradiologists or 3rd generation CT scanners are not easily accessible.

Effect of acute and short-term dietary fat ingestion on postprandial skeletal muscle protein synthesis rates in middle-aged, overweight, and obese men.

Muscle anabolic resistance to dietary protein is associated with obesity and insulin resistance. However, the contribution of excess consumption of fat to anabolic resistance is not well studied. The aim of these studies was to test the hypothesis that acute and short-term dietary fat overload will impair the skeletal muscle protein synthetic response to dietary protein ingestion. Eight overweight/obese men [46.4 ± 1.4 yr, body mass index (BMI) 32.3 ± 5.4 kg/m2] participated in the acute feeding study, which consisted of two randomized crossover trials. On each occasion, subjects ingested an oral meal (with and without fat emulsion), 4 h before the coingestion of milk protein, intrinsically labeled with [1-13C]phenylalanine, and dextrose. Nine overweight/obese men (44.0 ± 1.7 yr, BMI 30.1 ± 1.1 kg/m2) participated in the chronic study, which consisted of a baseline, 1-wk isocaloric diet, followed by a 2-wk high-fat diet (+25% energy excess). Acutely, incorporation of dietary amino acids into the skeletal muscle was twofold higher (P < 0.05) in the lipid trial compared with control. There was no effect of prior lipid ingestion on indices of insulin sensitivity (muscle glucose uptake, pyruvate dehydrogenase complex activity, and Akt phosphorylation) in response to the protein/dextrose drink. Fat overfeeding had no effect on muscle protein synthesis or glucose disposal in response to whey protein ingestion, despite increased muscle diacylglycerol C16:0 (P = 0.06) and ceramide C16:0 (P < 0.01) levels. Neither acute nor short-term dietary fat overload has a detrimental effect on the skeletal muscle protein synthetic response to dietary protein ingestion in overweight/obese men, suggesting that dietary-induced accumulation of intramuscular lipids per se is not associated with anabolic resistance.

Relative Contribution of Intramyocellular Lipid to Whole-Body Fat Oxidation Is Reduced With Age but Subsarcolemmal Lipid Accumulation and Insulin Resistance Are Only Associated With Overweight Individuals.

Insulin resistance is closely related to intramyocellular lipid (IMCL) accumulation, and both are associated with increasing age. It remains to be determined to what extent perturbations in IMCL metabolism are related to the aging process per se. On two separate occasions, whole-body and muscle insulin sensitivity (euglycemic-hyperinsulinemic clamp with 2-deoxyglucose) and fat utilization during 1 h of exercise at 50% VO2max ([U-(13)C]palmitate infusion combined with electron microscopy of IMCL) were determined in young lean (YL), old lean (OL), and old overweight (OO) males. OL displayed IMCL content and insulin sensitivity comparable with those in YL, whereas OO were markedly insulin resistant and had more than twofold greater IMCL in the subsarcolemmal (SSL) region. Indeed, whereas the plasma free fatty acid Ra and Rd were twice those of YL in both OL and OO, SSL area only increased during exercise in OO. Thus, skeletal muscle insulin resistance and lipid accumulation often observed in older individuals are likely due to lifestyle factors rather than inherent aging of skeletal muscle as usually reported. However, age per se appears to cause exacerbated adipose tissue lipolysis, suggesting that strategies to reduce muscle lipid delivery and improve adipose tissue function may be warranted in older overweight individuals.

Lipid-induced insulin resistance is associated with an impaired skeletal muscle protein synthetic response to amino acid ingestion in healthy young men.

The ability to maintain skeletal muscle mass appears to be impaired in insulin-resistant conditions, such as type 2 diabetes, that are characterized by muscle lipid accumulation. The current study investigated the effect of acutely increasing lipid availability on muscle protein synthesis. Seven healthy young male volunteers underwent a 7-h intravenous infusion of l-[ring-(2)H5]phenylalanine on two randomized occasions combined with 0.9% saline or 10% Intralipid at 100 mL/h. After a 4-h "basal" period, a 21-g bolus of amino acids was administered and a 3-h hyperinsulinemic-euglycemic clamp was commenced ("fed" period). Muscle biopsy specimens were obtained from the vastus lateralis at 1.5, 4, and 7 h. Lipid infusion reduced fed whole-body glucose disposal by 20%. Furthermore, whereas the mixed muscle fractional synthetic rate increased from the basal to the fed period during saline infusion by 2.2-fold, no change occurred during lipid infusion, despite similar circulating insulin and leucine concentrations. This "anabolic resistance" to insulin and amino acids with lipid infusion was associated with a complete suppression of muscle 4E-BP1 phosphorylation. We propose that increased muscle lipid availability may contribute to anabolic resistance in insulin-resistant conditions by impairing translation initiation.

Inhaled corticosteroids and bone health.

Inhaled corticosteroids (ICS) are the cornerstones in the management of bronchial asthma and some cases of chronic obstructive pulmonary disease. Although ICS are claimed to have low side effect profiles, at high doses they can cause systemic adverse effects including bone diseases such as osteopenia, osteoporosis and osteonecrosis. Corticosteroids have detrimental effects on function and survival of osteoblasts and osteocytes, and with the prolongation of osteoclast survival, induce metabolic bone disease. Glucocorticoid-induced osteoporosis (GIO) can be associated with major complications such as vertebral and neck of femur fractures. The American College of Rheumatology (ACR) published criteria in 2010 for the management of GIO. ACR recommends bisphosphonates along with calcium and vitamin D supplements as the first-line agents for GIO management. ACR recommendations can be applied to manage patients on ICS with a high risk of developing metabolic bone disease. This review outlines the mechanisms and management of ICS-induced bone disease.

Panniculitis in a patient presenting with a pancreatic tumour and polyarthritis: a case report.

INTRODUCTION: Panniculitis is a rare manifestation of pancreatic disease. Rarer still is the association of panniculitis, pancreatitic disease and polyarthritis. A literature search revealed less than five cases of pancreatic panniculitis associated with pancreatic tumour and polyarthritis. CASE PRESENTATION: An 84-year-old Caucasian man presented with epigastric pain, weight loss, polyarthritis and multiple discharging nodules. A computed tomography scan revealed a mass in the head of the pancreas. Histology of the cutaneous lesions confirmed the diagnosis of pancreatic panniculitis. CONCLUSION: Pancreatic panniculitis can clinically present in many ways to clinicians across a broad scope of specialties. Knowledge and understanding of the association between panniculitis and polyarthritis with pancreatic disease may aid rapid diagnosis and management.

The influence of chemical gustatory stimuli and oral anaesthesia on healthy human pharyngeal swallowing.

This study explored the effects of taste and oral anaesthesia on human sequential swallowing. Subjects were healthy adults (n = 42, mean age 28 years, 21 females), investigated by means of a water swallow test. Taste stimuli comprised quinine, glucose, citrus and saline solutions compared with neutral water. Oral anaesthesia comprised topical lidocaine at doses of 10, 20 and 40 mg and compared with placebo. Data were collected on swallowing speed (volume per second), inter-swallow interval and swallowing capacity (volume per swallow). Compared with water, glucose, citrus and saline reduced swallowing speed (10.94 +/- 0.89 versus 9.56 +/- 0.79, 9.33 +/- 1.19, 9.37 +/- 0.92 ml/s respectively, P < 0.05). Inter-swallow interval was increased only by quinine and saline (1.47 +/- 1.11 versus 2.13 +/- 0.34 and 1.92 +/- 0.31 s, P < 0.04). Swallowing capacity was only marginally increased by quinine (P = 0.0759). Compared with the placebo, only 40 mg of lidocaine altered swallowing, immediately reducing the swallowing speed (7.89 +/- 2.34 versus 10.11 +/- 3.26 ml/s, P < 0.05) and increasing inter-swallow interval (1.67 +/- 0.38 versus 1.45 +/- 0.29 s, P < 0.01) without affecting capacity. By 15 min all measures except sensory thresholds had returned to baseline values. Thus, swallowing function is highly influenced by chemosensory input, providing insight into how oral sensation regulates pharyngeal swallowing.